Haplo-Cord Transplantation for Blood Cancer

Not currently recruiting at 1 trial location

Overseen By Meredith Mullane, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Severely limited life expectancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to improve transplant outcomes for individuals with blood cancers and other blood disorders. It focuses on combining umbilical cord blood with stem cells from a family member to find better matches for patients. This approach aims to increase transplant success rates, particularly when a perfect donor match is unavailable. The trial seeks participants who have faced challenges with previous treatments for conditions like leukemia or lymphoma and require a stem cell transplant. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to benefit from innovative transplant strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since a chemotherapy conditioning regimen is involved, it's possible that some medications might need to be adjusted. It's best to discuss this with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that haplo-cord transplantation, which uses stem cells from a family member along with umbilical cord blood, is safe. Studies have found that this method helps blood cells recover faster and reduces some transplant-related risks. Approximately 60 people have undergone this combined transplant with promising results.

The treatments involved, such as the CliniMACS CD34 selection device and certain chemotherapy drugs, have been used in similar situations before and are generally well-tolerated. While no new experimental drugs are part of this study, the umbilical cord blood units remain under investigation. However, existing data reassures their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Haplo-Cord Transplantation for blood cancer because it combines umbilical cord blood with stem cells from a family donor, which is a new approach compared to standard options like chemotherapy and fully matched transplants. This method utilizes unlicensed cord blood units, considered investigational, which could potentially expand the donor pool and make transplants more accessible. Additionally, the use of the CliniMACS CD34 selection device to purify donor cells is a novel feature, enhancing the safety and effectiveness of the transplant process by reducing complications like graft-versus-host disease.

What evidence suggests that this trial's treatments could be effective for blood cancer?

In this trial, participants will receive stem cells purified using the CliniMACS CD34 Reagent System. Studies have shown that this system can make stem cell transplants more successful. It selects specific cells likely to grow and thrive in the patient's body, cleaning and purifying CD34+ cells, which are vital for producing new blood cells. Research indicates that this method helps these cells recover and remain pure, crucial for successful transplants. Additionally, past patients using this system have experienced positive results, suggesting it may improve transplant success rates. Overall, this technology is a promising tool for enhancing transplant outcomes in blood cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Alexandra Gomez Arteaga, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with various blood cancers or disorders needing a transplant, like leukemia, lymphoma, myeloma, and more. They should be in good enough health to tolerate the procedure (KPS >= 70%) and have acceptable organ function. It's not suitable for those who can find an exact donor match quickly, are pregnant or breastfeeding, have severe heart/lung problems, active hepatitis/cirrhosis, uncontrolled infections or HIV.

Inclusion Criteria

I have been diagnosed with chronic myelogenous leukemia in a specific phase.

I have been diagnosed with multiple myeloma.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Pregnant or lactating

My heart's pumping ability is severely reduced, or my lung tests show poor function.

I have long-term active hepatitis or cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Conditioning

Participants undergo a chemotherapy conditioning regimen prior to stem cell transplantation

2-3 weeks

Transplantation

Participants receive a haplo-cord transplantation, involving umbilical cord blood and haplo-identical stem cells

Immediate post-conditioning

Engraftment Monitoring

Participants are monitored for engraftment success and initial recovery post-transplant

100 days

Long-term Follow-up

Participants are monitored for long-term outcomes including survival, relapse, and transplant-related complications

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Anti-thymocyte globulin (rabbit)
• CliniMACS® CD34 Reagent System
• Fludarabine
• Melphalan
• Mycophenolate Mofetil
• Rituximab
• Tacrolimus
• Total Body Irradiation

Trial Overview The study tests whether matching a cord blood graft to inherited paternal antigens (IPAs) improves haplo-cord transplant outcomes compared to just focusing on cell dose. Participants receive stem cells from both umbilical cord blood and a half-matched family donor after chemotherapy conditioning but no experimental drugs are used.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 8 Interventions

All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.

Group II: Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg Experimental Treatment 8 Interventions

All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.

Group III: Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg Experimental Treatment 8 Interventions

All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.

Group IV: Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg Experimental Treatment 8 Interventions

All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

The addition of rabbit antithymocyte globulin to a low-dose conditioning regimen before hematopoietic stem cell transplantation may reduce the risk of graft-versus-host disease (GVHD), as indicated by a 40% incidence of acute GVHD in the study of 22 patients with hematologic malignancies.

Despite one case of graft rejection, the overall approach appears effective, with chronic GVHD developing in 9 of 14 patients who survived beyond 100 days, suggesting that this regimen can support successful transplantation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unrelated donor hematopoietic stem cell transplantation for patients with hematologic malignancies using a nonmyeloablative conditioning regimen of fludarabine, low-dose total body irradiation, and rabbit antithymocyte globulin. Rowley, SD., Goldberg, SL., Pecora, AL., et al.[2013]

In a phase II clinical trial involving 28 patients with severe aplastic anemia, a conditioning regimen of fludarabine, cyclophosphamide, and thymoglobulin led to successful donor-type hematologic recovery in all participants, indicating effective engraftment.

Despite the promising engraftment results, the study reported a high treatment-related mortality rate of 67.9%, with complications such as thrombotic microangiopathy and chronic GVHD, highlighting the need for further research to reduce these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful engraftment with fludarabine, cyclophosphamide, and thymoglobulin conditioning regimen in unrelated transplantation for severe aplastic anemia: A phase II prospective multicenter study. Kang, HJ., Shin, HY., Park, JE., et al.[2017]

In a study involving five patients with severe aplastic anemia, a conditioning regimen of fludarabine, cyclophosphamide, and thymoglobulin resulted in complete donor type hematologic recovery for all participants, indicating high efficacy for bone marrow transplantation.

The combination treatment showed minimal complications, with only one case of mild acute graft-versus-host disease (GVHD) and no serious complications, suggesting a favorable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. Kang, HJ., Shin, HY., Choi, HS., et al.[2013]

In a study of 29 patients receiving anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG) for aplastic anemia, 62.1% experienced adverse effects, with fever being the most common.

ATG, which is rabbit-derived, was associated with more frequent adverse effects compared to ALG, and shorter intervals between treatment cycles increased the risk of these reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of anti-thymocyte globulin/anti-lymphocyte globulin therapy]. Kobayashi, R., Kaneda, M., Watanabe, N., et al.[2006]

Haplo-cord transplantation using CD34+-selected partially matched unrelated donor grafts allows for rapid engraftment in patients lacking a suitable haploidentical donor, with 83% achieving cord blood unit (CBU) engraftment by day +60.

The procedure demonstrated a manageable safety profile, with a 27% incidence of grade 2-4 acute graft-versus-host disease (GVHD) and a 4% incidence of chronic GVHD at one year, while achieving an overall survival rate of 54% at one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood transplants supported by unrelated donor CD34+ progenitor cells. Gomez-Arteaga, A., Orfali, N., Guarneri, D., et al.[2021]

In a phase II study involving 16 patients with hematologic malignancies, the addition of rabbit antithymocyte globulin (rATG) to the fludarabine and busulfan conditioning regimen showed low rates of acute and chronic graft versus host disease (GvHD), which is a positive safety outcome.

The study found significant interpatient variability in pharmacologic biomarkers related to busulfan and fludarabine, suggesting that further research is needed to optimize the conditioning regimen for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot pharmacologic biomarker study of busulfan and fludarabine in hematopoietic cell transplant recipients. McCune, JS., Woodahl, EL., Furlong, T., et al.[2021]

In a study of 239 patients undergoing haploidentical hematopoietic cell transplant, the combination of low-dose post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) significantly reduced the incidence of severe acute graft-versus-host disease (GVHD) and non-relapse mortality compared to the standard ATG regimen.

The ATG/PTCy treatment improved GVHD-free, relapse-free survival rates, indicating its efficacy in preventing complications associated with transplant, although it was associated with slower recovery of blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. Wang, Y., Wu, DP., Liu, QF., et al.[2023]

In a study involving 34 adult patients with severe aplastic anemia undergoing haplo-identical stem cell transplantation, a conditioning regimen using 600 cGy total body irradiation, fludarabine, and intermediate-dose rabbit ATG resulted in successful primary engraftment for all patients.

The group receiving the lower dose of total body irradiation (600 cGy) showed a trend towards better overall survival (91.7%) and graft-versus-host disease (GVHD)-free survival (78.4%) compared to those receiving higher doses, indicating a potentially safer and more effective approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal conditioning regimen for haplo-identical stem cell transplantation in adult patients with acquired severe aplastic anemia: Prospective de-escalation study of TBI and ATG dose. Lee, SE., Park, SS., Jeon, YW., et al.[2019]

In a study of 122 AML patients, reduced intensity conditioning (RIC) using busulfan/fludarabine/low-dose total body irradiation (TBI) resulted in significantly lower rates of severe acute graft-versus-host disease (aGVHD) compared to myeloablative conditioning (MAC) with busulfan/fludarabine (6.2% vs 26.1%).

Both RIC and MAC regimens showed similar long-term outcomes in terms of overall survival, chronic GVHD, relapse rates, and non-relapse mortality, indicating that thymoglobulin used for GVHD prophylaxis did not adversely affect survival with the RIC regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxis. Modi, D., Singh, V., Kim, S., et al.[2021]

In a study of 78 patients with severe aplastic anemia, the combination of anti-human thymocyte immunoglobulin (ATG-F) and cyclosporin A (CsA) achieved a 100% effective rate, demonstrating its efficacy in treating the condition.

The combination therapy also significantly shortened the time for patients to show improvement compared to ATG-F alone, indicating a faster response to treatment while maintaining a reliable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of Rabbit Anti-human Thymocyte Immunoglobulin Combined with Cyclosporin A on Severe Aplastic Anemia]. Luo, W., Ji, LH., Geng, H., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03093844

Study Details | Haploidentical CD34+ Selected Cells ... This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7746597/

Engraftment Kinetics after Transplantation of Double Unit ... Grafts were CD34+ cell-selected using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Gladbach, Germany) under an Investigational New ...

3. withpower.com withpower.com/trial/phase-hematologic-diseases-9-2017-9c176

Haploidentical Transplant for Blood Disorders This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/11/NCT02162511/Prot_SAP_000.pdf

AN EXPANDED ACCESS STUDY USING THE CLINIMACS ... CliniMACS® CD34+ Reagent System has the advantages of the best T cell depletion efficiency achievable and a very high efficiency of CD34+ cell recovery so that ...

5. astctjournal.org astctjournal.org/article/S1083-8791(11)00350-8/fulltext

Characteristics of CliniMACS® System CD34-Enriched T ... Previously published data using the CliniMACS CD34 Reagent System have shown a better recovery and purity of CD34-enriched products using a system that results ...

6. astctjournal.org astctjournal.org/article/S2666-6367(25)01408-3/fulltext

Efficacy and Safety of Haploidentical Hematopoietic Stem ... Umbilical cord blood (UCB) infusion may mitigate these risks by promoting immune tolerance and hematopoietic recovery. However, the efficacy of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8882346/

Umbilical cord blood or HLA-haploidentical transplantation Consistent with the primary results of the trial, the risk of non-relapse mortality was higher after transplantation of two-unit UCB compared to Haplo-BM (HR ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01745913

Randomized HaploCord Blood Transplantation vs. Double ... The combined transplantation of haplo-identical stem cells and cord blood has previously been used in approximately 60 subjects with very encouraging results.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725014083

Efficacy and safety of haploidentical hematopoietic stem ... Haplo-HSCT combined with UCB infusion is a safe and effective strategy for patients lacking young donors, offering rapid hematopoietic recovery, ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38705885/

a multicenter, randomized, open-label, phase 3 trial Overall median follow-up was 36.50 months (IQR 24.75-46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% ...